Leflunomide for Maintenance of Remission in IgG4 Related Disease
Study Details
Study Description
Brief Summary
The study has been designed as a 12-month, open-label, randomized, controlled study comparing the use of prednisone mono-therapy and prednisone and leflunomide combination therapy in treating patients with IgG4-related disease.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
The aim of this clinical trial is to determine the safety and efficacy of Leflunomide in treating patients with IgG4-related disease by comparing the outcomes of prednisone and leflunomide combination therapy with prednisone mono-therapy. The follow-up period will be 12 months. During the follow-up period, results of laboratory tests and image examinations, IgG4-RD RI and other parameters which can reflect treatment response as well as adverse effect events will be recorded.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Prednisone Prednisone mono-therapy |
Drug: Prednisone
Prednisone:A starting dose of 0. 5-0. 8mg/(kg*d) will be given. Following four-week period, the dose will be tapered gradually to 5mg/d until the end of 12 months of follow-up period.
Other Names:
|
| Experimental: Prednisone and Leflunomide Prednisone and Leflunomide combination therapy |
Drug: Prednisone
Prednisone:A starting dose of 0. 5-0. 8mg/(kg*d) will be given. Following four-week period, the dose will be tapered gradually to 5mg/d until the end of 12 months of follow-up period.
Other Names:
Drug: Leflunomide
Leflunomide:A starting dose of 20 mg/day will be given. This dose may be decreased to 10 mg/day at the discretion of the treating physician if minor adverse effects occur(e.g., liver enzyme elevations).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Relapse rate at 12 months. [12 months]
Relapse referred to the recurrence of previous clinical manifestations or abnormality of organ-specific imaging findings or serology tests after remission.
Secondary Outcome Measures
- Relapse rate at 6 months. [6 months]
Relapse referred to the recurrence of previous clinical manifestations or abnormality of organ-specific imaging findings or serology tests after remission.
- Complete response assessed by IgG4-RD Responder Index (IgG4-RD RI) at 1, 3, 6 and 12 months. [Up to 12 months]
Complete response (CR) is defined as IgG4-RD RI <3 at 1, 3, 6 and 12 months.
- Partial response assessed by IgG4-RD RI at 1, 3, 6 and 12 months. [Up to 12 months]
Partial response (PR) is defined as IgG4-RD RI remaining ≥3 at 1, 3, 6 and 12 months.
- Serum IgG4 concentrations (mg/dL) measured by immunonephelometry at 1, 3, 6 and 12 months. [Up to 12 months]
- Number of circulating plasmablasts (cell number/mL) assessed by flow cytometry by gating peripheral blood at 1, 3, 6 and 12 months. [Up to 12 months]
- Adverse effect events [Up to 12 months]
Treatment-related adverse effect, including abnormal liver function and leukopenia.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age between 18 and 80 years.
-
Diagnosis of IgG4-RD according to either Consensus statement on the pathology of IgG4-related disease (for those who have undergone biopsies) or 2011 Comprehensive diagnostic criteria for IgG4-related disease. Both of the two criteria for diagnosis are specified below.
(1)Consensus statement on the pathology of IgG4-related disease
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Histopathologic features consisting of dense lymphoplasmacytic infiltrate, fibrosis(usually storiform in character)and/or obliterative phlebitis within involved organs.
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Either an elevated IgG4+/IgG+cell ratio of >40% within the affected organs or elevated IgG4-bearing plasma cells per high-power field is necessary. The cut-off number of IgG4-bearing plasma cells per high-power field is different depending upon the types of affected organs and specimens(through surgery or needle puncture biopsy).
(2)2011 Comprehensive diagnostic criteria for IgG4-related disease
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Clinical examination showing characteristic diffuse/localized swelling or masses in single or multiple organs.
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Hematological examination shows elevated serum IgG4 concentrations(135 mg/dl).
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Histopathologic examination shows marked lymphocyte and plasmacyte infiltration and fibrosis or Infiltration of IgG4+ plasma cells(ratio of IgG4+/IgG+ cells > 40% and >10 IgG4+ plasma cells/HPF).
Definite: a + b + c,Probable: a + c,Possible: a + b
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Excluded from malignant tumors of each organ (e.g. cancer, lymphoma) and similar diseases (e.g. Sjögren's syndrome, primary sclerosing cholangitis, Castleman's disease, secondary retroperitoneal fibrosis, Wegener's granulomatosis, sarcoidosis, Churg-Strauss syndrome) by additional histopathological examination.
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Even when patients cannot be diagnosed using the Comprehensive diagnostic criteria, they may be diagnosed using organ-specific diagnostic criteria for IgG4-RD, such as Diagnostic criteria for IgG4-Mikulicz's disease.
Exclusion Criteria:
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Subjects having received steroids or immunosuppressants in recent 3 months will be excluded.
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Subjects who were hypersensitive to leflunomide will be excluded.
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ALT and/or AST is more than two folds of the upper limit of relevant reference value at baseline.
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WBC is less than 3×10*9/L at baseline.
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Female patients who are pregnant or breastfeeding.
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Known significant concurrent medical disease.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Chinese PLA General Hospital | Beijing | China | 100000 |
Sponsors and Collaborators
- Chinese PLA General Hospital
Investigators
- Principal Investigator: Jian Zhu, Chinese PLA General Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ChinaPLAGH-IgG4